CNS catecholamines are thought to play an important role in human anxiety, mood, alertness, and cognition. The present studies were conducted in healthy volunteers to determine the role of catecholamines in the changes in alertness, mood, and cognitive performance associated with sleep deprivation. Treatment with alpha-methyl-para-tyrosine (AMPT), a catecholamine synthesis inhibitor, led to increases in anxiety and sleepiness as well as decreases in cognitive performance. These changes were significantly enhanced when AMPT-treated subjects were also subjected to 38.5 hours of total sleep deprivation. The effects of AMPT on anxiety and alertness were reversed by treatment with L-Dopa/ Carbidopa, indicating that AMPT's effects are catecholamine specific. Further, these findings support the view that catecholamines are important modulators of anxiety, alertness, and cognition, and suggest that catecholamine dysfunction may be the basis for some anxiety disorders.